Gene-environment interaction and susceptibility in head and neck cancer patients and in their first-degree relatives: a study of Northeast Indian population

Abstract

Background: The environmental and genetic factors are known to be associated with head and neck squamous cell carcinoma (HNSCC). Here, we investigated the GSTM1 and GSTT1 polymorphisms and tobacco uses in patients and in their first-degree relatives to evaluate susceptibility toward HNSCC. Further, we explored high-risk interaction between genetic and environmental risk factors.

Subjects and methods: Genotyping of GSTM1 and GSTT1 was performed in 170 patients, 300 first-degree relatives of patients and 300 controls using multiplex PCR. Multifactor dimensionality reduction (MDR) and logistic regression approach were applied for statistical analysis.

Results: Analysis revealed that GSTM1 and GSTT1 null genotype frequencies were significantly higher in patients (adjusted odds ratio (OR) = 2.18; P < 0.001 and OR = 1.61; P = 0.031, respectively). Also, the GSTM1 and GSTT1 null genotype frequencies were significantly higher in first-degree relatives of patients compared with controls (P = 0.004 and P = 0.041, respectively). In MDR analysis, the best model for HNSCC risk was four-factors model of tobacco, betel quid chewing, smoking and GSTM1 null genotypes (cross-validation consistency = 10/10 and P < 0.0001), whereas in interaction entropy graphs, tobacco chewing and GSTM1 null genotype further showed strongest synergistic interaction.

Conclusion: GSTM1 and GSTT1 null genotypes may act as markers to determine the genetic susceptibility in HNSCC patients and in their first-degree relatives. Furthermore, tobacco chewing and GSTM1 null genotype interaction identified as the strongest gene-environment model to predict HNSCC.

Keywords: GSTM1-GSTT1 polymorphism; MDR analysis; first-degree relatives; head and neck squamous cell carcinoma; tobacco habits.